Two Rab2 Interactors Regulate Dense-Core Vesicle Maturation

• A genetic screen for molecules involved in dense-core vesicle function
• Two conserved molecules, RUND-1 and CCCP-1, bind to activated RAB-2
• RUND-1, CCCP-1, and RAB-2 colocalize at the trans-Golgi network
• RAB-2, RUND-1, and CCCP-1 mediate sorting of dense-core vesicle cargos

SummaryPeptide neuromodulators are released from a unique organelle: the dense-core vesicle. Dense-core vesicles are generated at the trans-Golgi and then sort cargo during maturation before being secreted. To identify proteins that act in this pathway, we performed a genetic screen in Caenorhabditis elegans for mutants defective in dense-core vesicle function. We identified two conserved Rab2-binding proteins: RUND-1, a RUN domain protein, and CCCP-1, a coiled-coil protein. RUND-1 and CCCP-1 colocalize with RAB-2 at the Golgi, and rab-2, rund-1, and cccp-1 mutants have similar defects in sorting soluble and transmembrane dense-core vesicle cargos. RUND-1 also interacts with the Rab2 GAP protein TBC-8 and the BAR domain protein RIC-19, a RAB-2 effector. In summary, a pathway of conserved proteins controls the maturation of dense-core vesicles at the trans-Golgi network.